SALOME Clinical TrialQuestions and Answers

1. What was SALOME and what are the objectives of this study?
The Study to Assess Longer-term Opioid Medication Effectiveness (SALOME) is a clinical study that tests alternative treatments for people with chronic heroin addiction who are not benefiting sufficiently from available treatments such as oral methadone.

Studies in Canada and Europe have demonstrated that treatment with diacetylmorphine is more effective than oral methadone for some of the most vulnerable heroin users. HDM has now been shown to be as good as diacetylmorphine and should now become an alternative for those currently not benefitting from methadone and other treatments, and be integrated in the treatment continuum available through licensed doctors.

2. Who is eligible for SALOME?
Stringent controls were placed on the screening of participants to ensure that only those who fall within the “chronic” category were selected. The SALOME study defines “chronic” as persons with a history of at least five years of documented drug addiction. As well, participants must have been using heroin frequently for at least one year immediately prior to entry into the study.

The study had specific inclusion and exclusion criteria that were verified by lab testing, health care and pharmacy records to ensure the participation of the right candidates.

However, there are still hundreds of other patients that meet this criteria that could benefit from receiving hydromorphone or diacetylmorphine.

3. What about methadone? Isn’t that treatment effective enough?
Methadone and Suboxone are effective heroin addiction treatments for many people and should remain the first line response, but there are some people that don’t benefit from it.

Treatment with hydromorphone or diacetylmorphine under supervision is an intensified treatment option for people who have tried all other treatment options and continue injecting in the street. It is estimated that no more than 10% of all patients receiving substitution treatment will need to be treated in these clinics.

SALOME’s results underscore the importance of having as many treatment options as possible to address chronic heroin dependence and give another treatment choice for severely heroin-dependent individuals not benefitting from available treatments. Hydromorphone is another tool in the treatment toolbox.

4. How is the SALOME project being conducted?
SALOME involved two-stages, with each trial participant remaining for six months in each phase. In stage one, half of the 202 participants were randomized to receive injectable diacetylmorphine, while the other half received injectable HDM. This is a double-blind study — neither the participants nor the researchers or clinical team (other than the pharmacy) were aware of which treatment was being administered. In the second stage, half of the participants were randomized to continue injection treatment exactly as in stage one, while the other half switched to the oral equivalent of the same medication (diacetylmorphine or HDM). The oral version was also provided on a double-blind basis.

However, the oral version was discontinued due to futility. It became clear it would be highly unlikely for non-inferiority of the oral compared to the injectable arm to be concluded.

Once in the study, participants visited the clinic up to three times per day at which, after a pre-treatment assessment (for safety reasons), they received their medication. After injecting or ingesting their medication, participants were observed until staff determined that it was safe for them to leave. Addiction medicine doctors oversaw and monitored the prescriptions for both groups.

Throughout the treatment period, an interdisciplinary team of physicians, nurses, social workers and counselors were available to help participants achieve stability in their life, seek employment and find suitable housing. Some primary care services, HIV, Hepatitis C and psychiatric care were also provided. At any time, participants could choose to switch to methadone treatment, to drug-free (abstinence) programs, to detox programs or any other option available.

A research team conducted individual assessments to determine if the treatments were effective. This team worked closely but independently from the clinical team and had no power over clinical decisions.

5. Who was supervising this study?
The SALOME study received peer-reviewed scientific approval from the Canadian Institutes of Health Research as well as ethical approval from the University of British Columbia/Providence Health Care Ethics Board. SALOME also obtained permits and exemptions from Health Canada regarding the quality and safety of the medication and the clinical procedures. All of these organizations received yearly reports on the progress of the study. The study had a data and safety monitoring board comprised of independent experts that periodically reviewed data and made recommendations.

6. How was the study funded?
SALOME received funding from the Canadian Institutes of Health Research (CIHR) and private donors through the fundraising efforts of the InnerChange Foundation and St. Paul’s Hospital Foundation. The clinical care provided to participants in the study was funded by Providence Health Care. The total cost of the study was $7.4 Million.

7. Who made up the SALOME research team?
The study was headed by the Centre for Health Evaluation and Outcome Sciences (CHÉOS) at Providence Health Care researchers Drs. Eugenia Oviedo-Joekes and Michael Krausz. A leading addictions researcher, Dr. Oviedo-Joekes worked on a similar heroin prescription trial in Spain as well as Canada’s NAOMI project. Dr. Krausz has also worked in another heroin trial in Germany, the largest such randomized clinical trial in Europe.

The other co-investigators included Dr. Martin T. Schechter (NAOMI’s principal investigator), Drs. Aslam H. Anis, Nick Bansback, Suzanne Brissette, Julie Bruneau, and Christian Schultz, and Amin Janmohamed of the University of British Columbia, University of Montreal, and Providence Health Care.

8. When did the study conclude?
The study started in late 2011 and concluded in late 2015. The results have been published in the April 6th edition of the Journal of the American Medical Association (JAMA) Psychiatry.

9. Why did you reduce the number of participants required for the study? Will this compromise the quality of the research?
SALOME researchers wanted to see if the study questions in SALOME could be answered with a smaller number of participants, 202 instead of 322.

This would allow the study to be completed faster to provide the evidence that may support alternative treatments including a HDM program.

The SALOME Data Safety Monitoring Board (an independent group experts in the field including a statistician, addiction medicine specialist, ethicist, addiction policy specialist) agreed that the changed sample size of 202 has enough “power” to answer our study questions.

The study completed recruitment of all 202 participants and the treatment phase completed in early 2015.

10. Is mandatory counseling part of the study?
Study participants were offered and encouraged to participate in support services offered as part of the study.

Throughout the treatment period, an interdisciplinary team of physicians, nurses, social workers and counselors were available to help participants achieve stability in their life, seek employment and find suitable housing. Some primary care services, HIV, Hepatitis C and psychiatric care were also provided.

At any time, participants could choose to switch to methadone or suboxone treatment, to drug-free (abstinence) programs, to detox programs or any other option available.

11. What safety measures were in place to ensure the diacetylmorphine was not stolen?
For security purposes, we can’t go into the specifics regarding our security.

We have taken steps to ensure the security of the drugs.

The DAM is dispensed to individuals and must be ingested under the observation of trained health care professionals in the high-security medical clinic developed for the trial.

12. How are SALOME and NAOMI trials related?
The NAOMI study provided injectable HDM to a small group of participants. An unexpected finding was that many participants couldn’t tell the difference between the effects of diacetylmorphine and HDM.

However, the small number of participants receiving HDM did not permit researchers to draw any definite and scientifically valid conclusions as to the efficacy of HDM as a treatment option.

Therefore, the SALOME investigators designed a study to test this hypothesis.

SALOME aimed to determine alternative treatments for people with chronic heroin addiction not benefitting sufficiently from available treatments such as oral methadone.

13. Where does the diacetylmorphine come from?
It is pharmaceutical-grade diacetylmorphine manufactured by a pharmaceutical company outside Canada. It continues to be purchased and imported with permission from the Government of Canada. It is kept in a safe location.

14. Did the SALOME study add to public nuisance problems in Vancouver?
At the beginning of the study, researchers created a dedicated phone line for complaints about disruptions caused by the study or its participants. This line has never received a single call for SALOME. Researchers also put in place a neighbourhood and community advisory committee, which has helped with communication and consultation in the vicinity of the study.
This study has not posed any security concerns for residents or businesses in the surrounding community; nor has it increased drug trafficking and crime. In fact, it has had the opposite effect. Once people get stabilized they tend to become very orderly.

This study has not posed any security concerns for residents or businesses in the surrounding community; nor has it increased drug trafficking and crime. In fact, it has had the opposite effect. Once people get stabilized they tend to become very orderly.

SALOME Post-Trial

15. What happened to study participants after they completed their 12-months in the study?
They were no longer part of the study and become patients of PHC and/or VCH. They were offered ongoing treatment with the resources and medications that were available.

Participants and their doctor discussed the best treatment plan based on the available options.

Some of the patients needed diacetylmorphine, as no other treatment had worked for them. That’s why Providence doctors started submitting applications to the Special Access Programme (SAP) at Health Canada, requesting that they be allowed to prescribe diacetylmorphine to SALOME participants for compassionate use, which in their clinical judgement was a critical treatment for their patients.

As of March 16, 2016, 110 of these applications have been approved by Health Canada.

These approvals are limited to a treatment regime of 90 days.

Other participants were put on either oral or injectable hydromorphone.

16. Do you have a plan for making hydromorphone treatment available?
The results of SALOME were submitted to the Canadian Institutes for Health Research (CIHR) and Health Canada for review as well as published in the April 6th edition of the Journal of the American Medical Association (JAMA) Psychiatry.

As the results are positive, we are now in a position to pursue the licensing of hydromorphone as a substitution treatment for heroin dependency, adding another option for physicians and their patients alongside existing medication such as methadone, Suboxone and heroin-assisted treatment.

As a shorter-term solution, hydromorphone – currently licensed for use in pain relief – could be prescribed “off-label” as a heroin substitution treatment.

Doctors outside of PHC will now need to consider if they would be willing to prescribe HDM based on the results of SALOME alone, as international medical evidence is based on Diacetylmorphine (Heroin).

17. Does SALOME aim to promote legalization of heroin?
No. We are trying to find alternative treatments for people who have not benefited from methadone and other treatments. Treatment with medically prescribed opioids is a last resort for people who have tried all other treatment options without success.

Treatment with hydromorphone or diacetylmorphine under supervision is an intensified treatment option for people who have tried all other treatment options and continue injecting in the street. It is estimated that no more than 10% of all patients receiving substitution treatment will need to be treated in these clinics.

NAOMI Study

18. What was NAOMI?
NAOMI was North America’s first-ever clinical trial of prescribed heroin that took place from 2005 to 2008.

It was led by researchers from PHC and UBC, and tested whether medically prescribed heroin (diacetylmorphine) was more effective than methadone therapy for individuals with chronic heroin addiction who were not benefiting from other conventional treatments.

20. Who funded NAOMI and where was it conducted?
NAOMI was funded by the CIHR, Canada’s premier research funding agency, and was conducted at sites in Montreal and Vancouver. In Vancouver, this rigorous, controlled study was supervised by researchers at PHC and the University of British Columbia.

21. Who were the principal researchers in Vancouver?
The principal investigator/researcher on the NAOMI trial was Dr. Martin Schecter. The clinical lead for the Vancouver site of the NAOMI project was Dr. David Marsh.

22. How did people participate in the study?
Participants came to the clinic each day to receive their diacetylmorphine or methadone under the direct supervision of a doctor who specialized in addictions management.

23. Was mandatory counseling part of the study?
Study participants are offered and encouraged to participate in support services offered as part of the study.

Throughout the treatment period, an interdisciplinary team of physicians, nurses, social workers and counselors are available to help participants achieve stability in their life, seek employment and find suitable housing. Some primary care services, HIV, Hepatitis C and psychiatric care are also provided.

At any time, participants can choose to switch to methadone treatment, to drug-free (abstinence) programs, to detox programs or any other option available.

24. What did NAOMI find?
The NAOMI Trial results, published in the prestigious medical publication the New England Journal of Medicine, showed that participants treated with diacetylmorphine reported improved physical and mental health, were 62 per cent more likely to remain in addiction treatment and 40 per cent less likely to take illegal drugs and commit crimes to support their habit than were those treated with methadone.

After a year, 88 per cent of those treated with diacetylmorphine remained in treatment, compared with 54 per cent in the methadone group.

Data from NAOMI and other long-term studies with medically prescribed heroin show that many of the patients of these studies also transition from injection to oral treatments, detox programs and abstinence.

NAOMI Post-Study

25. What happened to the NAOMI participants after they completed the study?
Doctors were unable to secure approval from the federal government to give patients diacetylmorphine.

All participants who received injection medication were encouraged to switch to methadone.

Providence agreed to provide interim funding for the continued operations of a methadone program at the clinic site. SALOME was designed to continue the work of NAOMI.

International Studies and Programs

26. Have there been heroin-assisted treatment studies and programs in other countries?
Over the past 15 years, six trials comparing medically prescribed heroin and oral methadone (including NAOMI) have been conducted involving more than 1,500 patients. They provide strong evidence, both individually and collectively, in support of the effectiveness of treatment with fully supervised self-administered injectable heroin, when compared with oral methadone, for long-term heroin-dependent individuals. Studies have been conducted in six countries: Switzerland, the Netherlands, Spain, Germany, England and Canada.
Heroin-assisted treatment has been officially adopted in the United Kingdom, Switzerland, Germany, Denmark and the Netherlands.

Experts who further reviewed this data in 2011 concluded:
“The available evidence suggests an added value of heroin prescribed alongside flexible doses of methadone for long-term, treatment refractory, opioid users, to reach a decrease in the use of illicit substances, involvement in criminal activity and incarceration, a possible reduction in mortality; and an increase in retention in treatment. Due to the higher rate of serious adverse events, heroin prescription should remain a treatment for people who are currently or have in the past failed maintenance treatment, and it should be provided in clinical settings where proper follow-up is ensured.” -- Ferri M, Davoli M, Perucci CA. Interventions, Best Practice and Scientific Partners, European Monitoring Centre for Drugs and Drug Addiction, Cais do Sodre’ 1249-289 Lisbon, Lisbon, Portugal.

Opioid Treatment in General

27. What are opioids?
Doctors prescribe opioid medication to treat pain and sometimes for other health problems such as severe coughing. The medication comes in a pill, a liquid, or a wafer. It also comes in a patch worn on the skin. Examples of prescribed opioid medications include: codeine, OxyContin, HDM, morphine and methadone.

28. Are opioids addictive?
The pathway to addiction is complex, highly individual and often traumatic. People using heroin have often experienced traumatic events including childhood abuse and neglect, generational trauma from Residential Schools or poverty, dysfunctional family life, lack of access to education, employment and housing and abusive relationships.

For many users, heroin provides a form of self-medicated relief from both their emotional pain and social reality. Once addicted, heroin users have no choice but to keep on using heroin or experience dangerous withdrawal.

29. Can opioid addiction be treated?
Opioid addiction is a chronic illness, like heart disease or diabetes. A chronic disease is a medical condition for life. It cannot be cured, but it can be managed. A person with addiction can regain a healthy, productive life.

Treatment assists individuals to get through dangerous withdrawal symptoms, stabilizes their lives and gives them the opportunity to wean themselves off gradually and begin to deal with their underlying psychological and mental health issues that contribute to their addiction.

Heroin-Assisted Treatment (HAT)

30. What is HAT?
Prescription heroin treatment, known as diacetylmorphine or Heroin-Assisted Treatment (HAT), allows a doctor to prescribe pharmaceutical grade heroin to a patient. The drug is produced in a hygienic pharmaceutical laboratory. It is provided to the patient in a controlled environment, such as a specialized medical clinic, and is then injected by the patient under medical supervision. It is an addiction medicine doctor who prescribes the precise dose that the patient requires.

Research has unanimously shown that HAT, delivered in a clinical setting with appropriate safeguards and supports, is a more effective treatment for problematic heroin use than methadone and is also more cost-effective.

31. Is the intent for people who receive HAT to remain on government-supplied heroin for the rest of their lives?
HAT programs are based on the understanding that heroin addiction is a chronic illness, like heart disease or diabetes.

The relapsing nature of this condition means people go through different stages in their drug dependence along their life: abstinence, recovery, substitution treatment, etc.

This is highly dependent on the person’s individual circumstances, the social context and the available services in the community.

Data from long-term studies with diacetylmorphine in Europe and current HAT programs show many patients transition from injection to oral substitution and also to abstinence while some patients remain on this treatment for years.

32. How is this treatment different from a supervised injection site?
One of the goals of heroin assisted treatment is to remove patients from the illegal drug market. Participants receive treatment (diacetylmorphine - prescribed heroin) as well as social supports, so they will not need to engage in the illicit drug trade to feed their addiction.

Conversely, supervised injection sites are legally protected places where drug users consume pre-obtained illicit drugs in a safe, non-judgmental environment that also provides health care, counseling, and referrals to other health and social services, including drug treatment.

33. Is it possible to quantify how many people treated with HAT eventually stop needing this treatment?
In Switzerland, which now operates 23 HAT centres throughout the country, over 40% of those who leave HAT enter into an abstinence-based program.

34. How do heroin maintenance programs work for Aboriginal people?
Aboriginal people are over-represented among those who are severely affected by heroin addiction. They also report lower access to heroin addiction treatment compared to non-Aboriginal people.

Findings from NAOMI suggest that offering heroin-assisted treatment to long-term Aboriginal heroin users is an effective way of attracting and keeping them in treatment and of dramatically reducing their risk of HIV infection.

The PHC study titled “Characteristics and Response to Treatment among Aboriginal People Receiving Heroin-assisted Treatment” was published July 13, 2010 in the Canadian Journal of Public Health.

The data, which was collected from 251 participants (60 of them were Aboriginals) at sites in Vancouver and Montreal, showed that patients treated with injectable DAM were more likely to stay in treatment and more likely to reduce their use of illegal drugs and other illegal activities than patients treated with oral methadone.

The profiles were similar among Aboriginal and non-Aboriginal study participants except for higher HIV rates among the Aboriginal group (23.3 per cent and 8.3 per cent respectively).

35. Won’t heroin patients become addicted to HAT?
Patients taking HAT are already addicted to heroin from their street use, so no new addictions are created.

We believe that heroin addiction should be viewed in the same way as other chronic health conditions that require ongoing treatment and support.

HAT uses pharmaceutical grade medicines, like diacetylmorphine, to assist individuals to stabilize their lives and gives them the opportunity to wean themselves off gradually and begin to deal with their underlying psychological and mental health issues that contribute to their addiction.

36. Can be people function and work on HAT?
Just like methadone, people who are stable on heroin-assisted treatment should be able to do many job they are otherwise qualified to do. A person stabilized on the correct dose is not sedated, in withdrawal or euphoric. The most common description of how a person feels on HAT is “normal.”

37. This is an increased focus on harm reduction. Don’t we need more treatment?
This is treatment. Taking medication for heroin addiction is like taking medication to control heart disease or diabetes.

Treatment assists individuals to get through dangerous withdrawal symptoms, stabilizes their lives and gives them the opportunity to wean themselves off gradually and begin to deal with their underlying psychological and mental health issues that contribute to their addiction.

38. Since the drug will be given free to drug users, won’t there be a tendency to consume more?
No. Evidence from NAOMI and other international studies showed doses given to patients did not increase and in fact tend to level off or decrease. The majority of people want to reduce their dependency on medication not increase it.

39. Aren’t these programs dangerous? Are you concerned about patient safety?
We need to start recognizing that heroin addiction is a chronic illness, like heart disease or diabetes.

Taking medication for heroin addiction is like taking medication to control heart disease or diabetes.

Pharmaceutical heroin in its pure form is not harmful to the body; the street drug, however, may be poorly manufactured, stored or transported in infectious conditions, and is often adulterated with unknown and potentially dangerous substances.

Illicit heroin is a very dangerous street drug. Because it is of unknown dose and purity, people using the drug face the risk of infection, overdose and death. As it is illegal, many people using heroin avoid health care venues and inject the drug in unsafe circumstances, without medical supervision and potentially without access to clean injection equipment. This places heroin users at high risk of being infected by or transmitting HIV and other blood borne diseases like Hepatitis C. Using poorly controlled drugs in unsafe settings means that users often need emergency medical care or have complicated medical conditions requiring frequent hospitalization.